The present invention is directed toward the synthesis of novel antifungal agents prepared by biotransformation of known compounds Galbonolide A (Rustmicin) and Galbonolide B.
Galbonolide A (Rustmicin) and Galbonolide B were independently reported in 1985 by Takatoni et al., J. Antibiotics 38, 1807-1809 and Achenbach et al., J. Antibiotics 39, 1760-1764. Galbonolide B was originally isolated as a fungal metabolite from Micromonospora chalcea by Otake and from Streptomyces galbus by Achenbach, independently. The compounds exhibit antifungal activity against a number of fungi including Candida that is associated with human infections, and Botrytis cinerea and Puccinia graminis that are associated with plant infections.
Galbonolide B is claimed in Japanese patent JP 1667737 which issued on May 29, 1992. Galbonolide A is claimed in Japanese patent JP 1667724 which also issued on May 29, 1992. No analogs of Galbonolide A or B have been claimed.
Unfortunately, Galbonolide A is chemically unstable. To prepare more stable analogues with potentially useful antifungal activities, a biotransformation process was used to modify known Galbonolides. As a result, two hydroxylated analogues of parent Galbonolides A and B were synthesized.